Publications

PURPOSE

To investigate the prognostic value of quantitative computed tomographic (CT) scoring for the extent of fibrosis or emphysema in the context of a clinical model that includes the gender, age, and physiology ( GAP gender, age, and physiology model) of the patient.

MATERIALS AND METHODS

Study cohorts were approved by local institutional review boards, and all patients provided written consent. This was a retrospective cohort study that included 348 patients (246 men, 102 women; mean age, 69 years ± 9) with idiopathic pulmonary fibrosis from two institutions. Fibrosis and emphysema visual scores were independently determined by two radiologists. Models were based on competing risks regression for death and were evaluated by using the C index and reclassification improvement.

RESULTS

The CT- GAP gender, age, and physiology model (a modification of the original GAP gender, age, and physiology model that replaces diffusion capacity of carbon monoxide with CT fibrosis score) had accuracy comparable to that of the original GAP gender, age, and physiology model, with a C index of 70.3 (95% confidence interval: 66.4, 74.0); difference in C index compared with the GAP gender, age, and physiology model of -0.4 (95% confidence interval: -2.2, 3.4). The performance of the original GAP gender, age, and physiology model did not change significantly with the simple addition of fibrosis score, with a change in C index of 0.0 (95% confidence interval: -1.8, 0.5) or of emphysema score, with a change in C index of 0.0 [95% confidence interval: -1.3, 0.4]).

CONCLUSION

CT fibrosis score can replace diffusion capacity of carbon monoxide test results in a modified GAP gender, age, and physiology model (the CT- GAP gender, age, and physiology model) with comparable performance. This may be a useful alternative model in situations where CT scoring is more reliable and available than diffusion capacity of carbon monoxide.

Children whose mothers are victims of intimate partner violence (IPV) are at increased risk of adverse health and psychosocial consequences, including becoming victims or perpetrators of violence in their own relationships. This study aimed to understand the role mothers may play in preventing the perpetuation of violence in their children's lives. We performed semistructured interviews with 18 IPV victims who are mothers and were living at the Women's Center & Shelter of Greater Pittsburgh from July through November 2011. We sought to understand how they communicate with their children about IPV and relationships. These mothers described a desire to explain their IPV experience and offer advice about avoiding violence in relationships. As foundations for these discussions, they emphasized the importance of close relationships and open communication with their children. Although mothers are interested in talking about IPV and relationships and identify communication strategies for doing so, many have never discussed these topics with their children. These mothers need and want an intervention to help them learn how to communicate with their children to promote healthy relationships. Development of a program to facilitate communication between IPV victims and their children could create an important tool to empower mothers to break the cross-generational cycle of domestic violence.

Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta-analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers.

During Mycobacterium tuberculosis and other respiratory infections, optimal T cell activation requires pathogen transport from the lung to a local draining lymph node (LN). However, the infected inflammatory monocyte-derived dendritic cells (DCs) that transport M. tuberculosis to the local lymph node are relatively inefficient at activating CD4 T cells, possibly due to bacterial inhibition of antigen presentation. We found that infected migratory DCs release M. tuberculosis antigens as soluble, unprocessed proteins for uptake and presentation by uninfected resident lymph node DCs. This transfer of bacterial proteins from migratory to local DCs results in optimal priming of antigen-specific CD4 T cells, which are essential in controlling tuberculosis. Additionally, this mechanism does not involve transfer of the whole bacterium and is distinct from apoptosis or exosome shedding. These findings reveal a mechanism that bypasses pathogen inhibition of antigen presentation by infected cells and generates CD4 T cell responses that control the infection.

Bartonella henselae is increasingly associated with a variety of pathological entities, which are often similar in dogs and human patients. Following an acute flea infestation, a dog developed an unusual clinical presentation for canine bartonellosis. Comprehensive medical, microbiological, and surgical interventions were required for diagnosis and to achieve a full recovery.

This study investigated the correspondence among four groups of raters on adherence to STAGE-12, a manualized 12-step facilitation (TSF) group and individual treatment targeting stimulant abuse. The four rater groups included the study therapists, supervisors, study-related ("TSF expert") raters, and non-project related ("external") raters. Results indicated that external raters rated most critically mean adherence - the mean of all the adherence items - and global performance. External raters also demonstrated the highest degree of reliability with the designated expert. Therapists rated their own adherence lower, on average, than did supervisors and TSF expert raters, but therapist ratings also had the poorest reliability. Findings highlight the challenges in developing practical, but effective methods of fidelity monitoring for evidence based practice in clinical settings. Recommendations based on study findings are provided.

Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.